No evidence that human GIGYF2 interacts with GRB10: implications for human disease.

GIGYF2 (growth factor receptor-bound protein 10 [GRB10]-interacting GYF [glycine-tyrosine-phenylalanine] protein 2) reduces mRNA stability and translation via microRNAs, ribosome quality control, and several RNA-binding proteins. GIGYF2 was first identified in mouse cell lines as an interacting partner with GRB10, which binds to the insulin receptor and the insulin-like growth factor ...
receptor 1. Mutations in the human GIGYF2 gene were reported in autism. In mouse models, Gigyf2 mutations engender several diseases. It was therefore thought that the GIGYF2-associated disease in humans is caused by defective GRB10 signaling. We show here that GIGYF2 does not interact with GRB10 in human cell lines, as determined by co-immunoprecipitation and proximity ligation assays. The lack of interaction is explained by the absence of the critical GYF domain-binding PPG? sequence in the human GRB10 protein. These results contrast with the current understanding that a GIGYF2/GRB10 complex is associated with human disease via insulin receptor and insulin-like growth factor receptor 1 signaling and underscore alternative mechanisms responsible for the observed phenotypes associated with mutations in the human GIGYF2 gene.
Mesh Terms:
Animals, Carrier Proteins, Cell Line, GRB10 Adaptor Protein, HEK293 Cells, Humans, Mice, Mutation, Protein Binding, Signal Transduction
Life Sci Alliance
Date: Sep. 01, 2025
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